• PhD, Department of Medicine, University of Birmingham (1992)
• BA (Hons) Natural Sciences (Genetics), University of Cambridge, UK (1987)

Andy Clark studied Natural Sciences at the University of Cambridge before doing a PhD in transcriptional regulation of insulin genes at the University of Birmingham. He continued his research at the University of Birmingham for two years, funded by a fellowship from Diabetes UK, before moving to the Cancer Research UK labs in Lincoln’s Inn Fields for three years. He then worked for almost sixteen years at the Kennedy Institute of Rheumatology, Imperial College London, first as a lecturer, then senior lecturer, then reader. In 2012 Andy was appointed as Professor of Inflammation Biology at the University of Birmingham.

• MSc in Immunology and Immunotherapy - Module lead for Inflammation and Cell Migration
• BMedSc - three lectures in “Cellular Pathology” and “Rheumatology and Orthopaedics” modules

• Andy supervises laboratory-based research projects for the MSc in Immunology and Immunotherapy
• Andy has supervised thirteen PhD students to award of degree. Most of these students are still in medical or scientific careers, some in industry, others in academia

Andy is interested in supervising doctoral research students in the following areas:

• Transcriptional and post-transcriptional gene regulation in the inflammatory response
• The biology of macrophages in the rheumatoid synovium
• Anti-inflammatory mechanisms of action of glucocorticoids and interleukin 10

If you are interesting in studying any of these subject areas please contact Andy at the contact details above, or for any general doctoral research enquiries, please email: dr@contacts.bham.ac.uk or call +44 (0)121 414 5005.

For a full list of available Doctoral Research opportunities, please visit our Doctoral Research programme listings

RESEARCH THEMES

Inflammation, Resolution, Rheumatology, Gene expression.

RESEARCH ACTIVITY

Control of mRNA stability

Inflammatory mediators such as tumour necrosis factor a (TNFa) are potentially harmful. Their expression is tightly regulated and normally occurs in a transient manner, with rapid induction by a pro-inflammatory stimulus followed by a rapid return to baseline. This pattern of gene expression is dependent on dynamic regulation of mRNA stability. We have characterised a phosphorylation-mediated switch that controls the stability of TNFa and many other pro-inflammatory mRNAs. We recently showed that this switch can be targeted to prevent different forms of experimentally-induced inflammatory pathology. Translational implications of these discoveries are being explored.

Feedback nodes

Resolution of inflammation is partly dependent on negative feedback loops, which ensure that responses to pro-inflammatory stimuli are both transient and proportional. For example, pro-inflammatory stimuli activate the MAPK p38 signalling pathway, promoting expression of inflammatory mediators such as TNFa At the same time, the expression of Dual Specificity Phosphatase 1 (DUSP1) is induced. DUSP1 inactivates p38 to terminate the inflammatory response. Negative feedback mechanisms such as this can also be exploited by anti-inflammatory agonists. For example, the expression of DUSP1 is enhanced and extended by anti-inflammatory glucocorticoids, and this results in more rapid and effective inactivation of inflammatory mediator gene expression. We refer to genes that behave like DUSP1 as “Feedback Node Genes”. Their cooperative regulation by both pro- and anti-inflammatory stimuli is poorly understood, but seems to play a major role in limiting inflammation and preventing chronic inflammatory pathology. We are investigating various Feedback Node Genes and trying to understand the basis of their cooperative regulation.

• Member of the Population and Systems Biology Board of the Medical Research Council
• Member of the Editorial Board of the Journal of Biological Chemistry
• Member of the Science Committee of the Society for Endocrinology

Rahman MM, Rumzhum NN, Hansbro PM, Morris JC, Clark AR, Verrills NM and Ammit AJ (2016) Activating protein phosphatase 2A (PP2A) enhances tristetraprolin (TTP) anti-inflammatory function in A549 lung epithelial cells. Cell Signal 28(4):325-34

Ross EA, Smallie T, Ding Q, O’Neil JD, Cunliffe HE, Tang T, Rosner DR, Klevernic I, Morrice NA, Monaco C, Cunningham AF, Buckley CD, Saklatvala J, Dean JL and Clark AR (2015) Dominant suppression of inflammation via targeted mutation of the mRNA destabilizing protein tristetraprolin. J Immunol 195(1):265-76

Smallie T, Ross EA, Ammit AJ, Cunliffe HE, Tang T, Rosner DR, Ridley ML, Buckley CD, Saklatvala J, Dean JL and Clark AR (2015) Dual-specificity phosphatase 1 and tristetraprolin cooperate to regulate macrophage responses to lipopolysaccharide. J Immunol 195(1):277-88

Rahman MM, Rumzhum NN, Morris JC, Clark AR, Verrills NM and Ammit AJ (2015) Basal protein phosphatase 2A activity restrains cytokine expression: role for MAPKs and tristetraprolin. Nature Scientific Reports 5:10063

Prabhala P, Bunge K, Rahman MM, Ge Q, Clark AR and Ammit AJ (2015) Temporal regulation of cytokine mRNA expression by tristetraprolin: dynamic control by p38 MAPK and MKP-1. Am J Physiol Lung Cell Mol Physiol 308(9):L973-80

Misharin AV, Cuda CM, Saber R, Turner J, Gierut AK, Haines GK, Berdnikov S, Filer A, Clark AR, Buckley CD, Mutlu GM, Budinger GRS and Perlman H (2014) Non-classical Ly6C- monocytes drive the development of inflammatory arthritis in mice. Cell Reports 9(2):591-604

Pinart M, Hussain F, Shirali S, Li F, Zhu J, Clark AR, Ammit AJ and Chung KF (2014) Role of mitogen-activated protein kinase phosphatase-1 in corticosteroid insensitivity of chronic oxidant lung injury. Eur J Pharmacol 744:108-14

Iqbal MB, Johns M, Liu Y, Yu S-C, Hyde GD, Laffan MA, Marchese FP, Cho SH, Clark AR, Gavins FN, Blackshear PJ, Wollard KJ, Mackman N, Dean JLE, Boothby M and Haskard DO (2014) PARP-14 combines with tristetraprolin in the selective posttranscriptional control of macrophage tissue factor expression. Blood 124:3646-55

Clark AR and Dean JLE (2012) The p38 MAPK pathway in rheumatoid arthritis: a sideways look. Open Rheumatology Journal 6:209-19

Ahasan M, Hardy R, Jones C, Kaur K, Hassan-Smith Z, Bénézech C, Caamaňo JH, Hewison M, Lavery G, Rabbitt EH, Clark AR, Buckley CD, Raza K, Stewart PM and Cooper MS (2012) Inflammatory regulation of glucocorticoid metabolism in mesenchymal stromal cells. Arthritis and Rheumatism 64(7):2404-13

Clark AR and Belvisi MG (2012) Maps and legends: the quest for dissociated ligands of the glucocorticoid receptor. Pharmacol Ther 134(1):54-67

Vattakuzhi Y, Abraham S, Freidin A, Clark AR* and Horwood N* (2012) Dual-specificity phosphatase 1-null mice exhibit spontaneous osteolytic disease and enhanced inflammatory osteolysis in experimental arthritis. Arthritis and Rheumatism 64(7):2201-10 *equal contributors

Turpeinen T, Nieminen R, Taimi V, Heittola T, Sareila OT, Clark AR, Moilanen E and Korhonen R (2012) Dual specificity phosphatase 1 regulates human inducible nitric oxide synthase expression by p38 MAP kinase. Mediators of Inflammation 127587

Joanny E, Ding Q, Gong L, Kong P, Saklatvala J and Clark AR (2012) Anti-inflammatory effects of selective glucocorticoid receptor modulators are partially dependent on up-regulation of dual specificity phosphatase 1. B J Pharmacol 165(4b):1124-36